Tissue Mechanics Regulate Mitotic Nuclear Dynamics during Epithelial Development.

Cell divisions are essential for tissue growth. In pseudostratified epithelia, where nuclei are staggered across the tissue, each nucleus migrates apically before undergoing mitosis. Successful apical nuclear migration is critical for planar-orientated cell divisions in densely packed epithelia. Most previous investigations have focused on the local cellular mechanisms controlling nuclear migration. Inter-species and inter-organ comparisons of different pseudostratified epithelia suggest global tissue architecture may influence nuclear dynamics, but the underlying mechanisms remain elusive. Here, we use the developing Drosophila wing disc to systematically investigate, in a single epithelial type, how changes in tissue architecture during growth influence mitotic nuclear migration. We observe distinct nuclear dynamics at discrete developmental stages, as epithelial morphology changes. We use genetic and physical perturbations to show a direct effect of cell density on mitotic nuclear positioning. We find Rho kinase and Diaphanous, which facilitate mitotic cell rounding in confined cell conditions, are essential for efficient apical nuclear movement. Perturbation of Diaphanous causes increasing defects in apical nuclear migration as the tissue grows and cell density increases, and these defects can be reversed by acute physical reduction of cell density. Our findings reveal how the mechanical environment imposed on cells within a tissue alters the molecular and cellular mechanisms adopted by single cells for mitosis

Relationship between the development of precore and core promoter mutations and hepatitis B e antigen seroconversion in patients with chronic hepatitis B virus

Chinese patients with chronic hepatitis B virus (332 with and 44 without cirrhosis-related complications) were studied. Fifty percent of patients <30 years old had precore mutations. The prevalence of precore mutations among hepatitis B e antigen (HBeAg)-positive patients, although lower than that among anti-HBe-positive patients (P = .031), was already high (44.2%). Median HBV DNA level in anti-HBe-positive patients was 1.5 × 106-1.55 × 106 copies/mL, irrespective of the presence or absence of precore mutations. There was no difference in the prevalence of precore mutations between patients with and without complications (P, not significant). However the prevalence of core promoter mutations was higher among patients with complications than among those without complications (90.5% vs. 69.3%, respectively; P = .003). In conclusion, precore mutations occurred in a large proportion of Chinese patients with chronic hepatitis B virus before HBeAg seroconversion. The development of complications was not related to precore mutations but was probably due to the persistence of significant viremia after HBeAg seroconversion.published_or_final_versio

Prognostic factors in severe exacerbation of chronic hepatitis B

Forty-seven patients with severe hepatitis B exacerbation were compared with patients who had mild exacerbation (n = 96) or no exacerbation (n = 96). Seventeen patients (36.2%) died or underwent liver transplantation. Preexisting cirrhosis and a prothrombin time (PT) of >30 s were associated with adverse outcome in 60.9% and 87.5% of patients, respectively. The rate of adverse outcome increased to 92.3% when albumin levels of ≤35 g/L and bilirubin levels of >200 μM were present. Other factors associated with adverse outcomes included peak bilirubin level, peak PT, time to reach peak PT, and the presence of encephalopathy and/or ascites. There was no difference in the frequency of precore mutations in patients with severe or mild exacerbation or without exacerbation. A significantly lower prevalence of core promoter mutants was found in patients with severe exacerbation (50%), compared with those who had mild exacerbation (81.3%; P = .004). Patients with severe exacerbation of hepatitis B with poor prognostic factors should be considered for early liver transplantation.published_or_final_versio

Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use

Background: The role of gastric acid suppression in preventing the recurrence of ulcer complications after the eradication of Helicobacter pylori infection in patients taking long-term low-dose aspirin is uncertain. Methods: We enrolled 123 patients who had ulcer complications after using low-dose aspirin continuously for more than one month and who had H. pylori infection. After the ulcers had healed and the H. pylori infection was eradicated, the patients were randomly assigned to treatment with 30 mg of lansoprazole daily or placebo, in addition to 100 mg of aspirin daily, for 12 months. The primary end point was the recurrence of ulcer complications. Results: During a median follow-up of 12 months, 9 of the 61 patients in the placebo group (14.8 percent), as compared with 1 of the 62 patients in the lansoprazole group (1.6 percent), had a recurrence of ulcer complications (adjusted hazard ratio, 9.6; 95 percent confidence interval, 1.2 to 76.1). Of these 10 patients, 4 had evidence of a recurrence of H. pylori infection and 2 had taken nonsteroidal antiinflammatory drugs before the onset of complications. Patients in the lansoprazole group were significantly less likely to have a recurrence of ulcer complications than patients in the placebo group (P=0.008). There was no significant difference in mortality between the two groups. Conclusions: In patients who had ulcer complications related to the long-term use of low-dose aspirin, treatment with lansoprazole in addition to the eradication of H. pylori infection significantly reduced the rate of recurrence of ulcer complications. Copyright © 2002 Massachusetts Medical Society.published_or_final_versio

Nonlinear ac response of anisotropic composites

When a suspension consisting of dielectric particles having nonlinear characteristics is subjected to a sinusoidal (ac) field, the electrical response will in general consist of ac fields at frequencies of the higher-order harmonics. These ac responses will also be anisotropic. In this work, a self-consistent formalism has been employed to compute the induced dipole moment for suspensions in which the suspended particles have nonlinear characteristics, in an attempt to investigate the anisotropy in the ac response. The results showed that the harmonics of the induced dipole moment and the local electric field are both increased as the anisotropy increases for the longitudinal field case, while the harmonics are decreased as the anisotropy increases for the transverse field case. These results are qualitatively understood with the spectral representation. Thus, by measuring the ac responses both parallel and perpendicular to the uniaxial anisotropic axis of the field-induced structures, it is possible to perform a real-time monitoring of the field-induced aggregation process.Comment: 14 pages and 4 eps figure

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio

Size Effect on Failure of Pre-stretched Free-Standing Nanomembranes

Free-standing nanomembranes are two-dimensional materials with nanometer thickness but can have macroscopic lateral dimensions. We develop a fracture model to evaluate a pre-stretched free standing circular ultrathin nanomembrane and establish a relation between the energy release rate of a circumferential interface crack and the pre-strain in the membrane. Our results demonstrate that detachment cannot occur when the radius of the membrane is smaller than a critical size. This critical radius is inversely proportional to the Young’s modulus and square of the pre-strain of the membrane

The counselling self-estimate inventory (COSE): Does it work in Chinese counsellors?

Counselling self-efficacy is an important construct for research and evaluation in counsellors' competencies and training effectiveness. Larson et al. developed the Counselling Self-Estimate Inventory (COSE) for counsellors in America and examined its factor structure using exploratory factor analysis. They recommended a five-factor model (microskills, counselling process, difficult client behaviour, cultural competence, and awareness of values) and the use of the COSE for future research. However, little research has investigated the validity of the COSE in the context of counselling Chinese students in schools. In the present study, the factor structure of responses to the Chinese version of the Counselling Self-Estimate Inventory in a sample of 578 Hong Kong secondary school guidance teachers was examined using the EQS approach to confirmatory factor analysis. The results showed that while a five-factor model was fairly able to fit the data, the deletion of items related to the awareness of values factor yielded a better fitting model. The discussion of potential uses and limitations of the C-COSE in the context of preparing and supervising school guidance personnel in student counselling is relevant to counselling psychologists and researchers in Hong Kong and other parts of the world.postprin